Among hyper-mutated GBMs, two cases had POLE mutations: an IDH-wt GBM from a 66 year old patient (TGCA-14-1795-01) which had 343 mutations and POLE Asp1123Asn mutation with unknown significance; a giant cell IDH-wt GBM from a 48 year old patient (case 19-1787-01) which had 576 mutations and POLE Ala399Val mutation reported of uncertain significance in the ClinVar database. The gene discussed is POLE; the disease is glioblastoma.